Radio-immunotherapy dose-painting (RAID) treatment for hormonal resistant prostate cancer

放射免疫治疗剂量涂抹 (RAID) 治疗激素抵抗性前列腺癌

• 批准号: 10484689
• 负责人: Wilfred Ngwa
• 金额: $ 39.97万
• 依托单位: NANOCAN THERAPEUTICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-09 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10484689
• 关键词: Abdomen; Address; Africa; Animals; Anti-CD40; Antigen-Presenting Cells; Antigens; Area; Biocompatible Materials; Biopsy; Bypass; Cancer Patient; Case Report Form; Certification; Chemotherapy and/or radiation; Clinical; Clinical Research; Clinical Trials; Collaborations; Community Hospitals; Cyclic GMP; Cytotoxic T-Lymphocytes; Dana-Farber Cancer Institute; Data; Data Collection; Databases; Development; Diagnosis; Diagnostic; Disease; Disease Resistance; Distant; Dose; Drug Delivery Systems; Drug Kinetics; Edema; Goals; Health; Health Services Accessibility; Hormonal; Human; Image; Immune; Immune system; Immunity; Immunotherapy; Indolent; Infrastructure; Institutes; Institutional Review Boards; Intervention; Intravenous; Lymphatic System; Malignant Neoplasms; Malignant neoplasm of prostate; Manufactured Materials; Medical; Medicine; Metastatic Neoplasm to the Bone; Metastatic Prostate Cancer; Metastatic to; Military Hospitals; Monitor; Monkeys; Mus; Nature; Needles; Neoplasm Metastasis; Newly Diagnosed; Outcome; Pain; Patients; Pelvis; Penetration; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Population; Preparation; Primates; Process; Production; Prostate; Prostatic Neoplasms; Protocols documentation; Quality of life; Radiation therapy; Radioimmunotherapy; Randomized; Research; Research Design; Research Project Grants; Resistance; Resource-limited setting; Resources; Safety; Schedule; Seeds; Site; Sterility; Structure; System; Systemic disease; T-Lymphocyte; Technology; Testing; Therapeutic; Time; Toxic effect; Translating; Visit; Work; arm; cancer care; cancer health disparity; cancer type; cell killing; chemotherapy; cost; design; disorder control; disparity reduction; draining lymph node; immunogenic; immunogenicity; improved; in situ vaccination; innovation; irradiation; male; nanoparticle; neoantigens; neoplastic cell; novel; open label; palliative; pre-clinical; premature; recruit; safety testing; side effect; standard of care; symptom treatment; treatment duration; tumor; ultrasound

ABSTRACT Prostate cancer, rather indolent by nature, has specific subtypes present with aggressive locoregional disease that are quickly becoming hormonal resistant. Patients with castrate-resistant disease (CRPC) are generally younger and non-Caucasian, and many suffer from local progression, edema, and pain. Radiotherapy (RT) is offered but limited by the extent, former exposure, and resistance of disease. Sequential multiple chemotherapy or RT treatments, offered as standard of care, are hard to comply to, especially in low-resource populations. Treatment of this symptomatic population is often terminated prematurely, or never started, due to financial and time restrictions. Innovative, shorter more efficient treatments are needed, especially to reduce disparities in compliance and outcomes of global cancer care. In extensive preclinical work, the combination of RT with immunogenic smart radiotherapy materials (iSRBs), addressed as radio-immunotherapy dose-painting (RAID) technology, brings intra-tumoral slow-release antiCD40 payload in the target that gets irradiated and has shown to prime the immune system and create sustainable tumor control by in situ-vaccination, even after different therapeutic options have failed. Moreover, this combination treatment can improve quality of life (QoL) fast by a short simple intervention with fewer side effects, having an antiCD40 payload far smaller than needed in intravenous (IV) immunotherapy. The overall goal of this project - proposed by Nanocan Therapeutics Corporation in collaboration with John Hopkins Medicine, Dana-Farber Cancer Institute and Northwell Health - is to bridge preclinical work to the first clinical trial with the innovative RAID technology and confirm its potential for in situ-vaccination that can extend the use of radiotherapy (RT) from palliative local treatment to systemic disease control in one session. The iSRBs are as seed-like fiducial markers administered directly in the prostate tumor by ultrasound guided needles. The iSRBs create contrast on CT and KV imaging making RT set-up fast; iSRBs slowly release (20mcg per unit over 15 days) anti-CD40 payload directly the target which gets irradiated, triggering in situ-vaccination. The purpose of this project is to translate extensive safety and efficacy data from small animal studies of single fraction RT combined with slow released intra-tumoral antiCD40 delivery to a first human trial for CRPC patients. The first part will be used to optimize iSRBs into a cGMP product, and confirmation of larger volume testing in monkeys to confirm safety, immunogenicity, and pharmacokinetics already performed in extensive small animal work. Milestones will complete IND filling by Nanocan Therapeutics. After FDA approval, second part of the project will encompass the Phase 1 single arm open label clinical trial seeking confirmation of safety and number of iSRBs as well as RT dose needed in CRPR patients. This project can provide all needed data for planned Phase II clinical work in aims offering a novel treatment paradigm for CRPR patients.

抽象的 前列腺癌本质上相当惰性，具有伴有侵袭性局部疾病的特定亚型 很快就会对荷尔蒙产生抵抗力。患有去势抵抗性疾病（CRPC）的患者通常 年轻人和非白种人，许多人患有局部进展、水肿和疼痛。放射治疗 (RT) 是 提供但受到疾病程度、以前的暴露和抵抗力的限制。序贯多次化疗 作为标准护理提供的放疗或放疗治疗很难遵守，尤其是在资源匮乏的人群中。 由于经济和经济原因，对这一有症状人群的治疗常常被提前终止或从未开始。 时间限制。需要创新、更短、更有效的治疗方法，特别是为了减少治疗方面的差异 全球癌症护理的合规性和结果。 在广泛的临床前工作中，放疗与免疫原性智能放疗材料（iSRB）的结合， 被称为放射免疫治疗剂量涂抹（RAID）技术，带来瘤内缓释 受到辐射的目标中的抗CD40有效负载已被证明可以启动免疫系统并产生 即使在不同的治疗方案失败后，也可以通过原位疫苗接种来可持续地控制肿瘤。而且， 这种联合治疗可以通过较少副作用的简短干预来快速提高生活质量 (QoL) 其抗CD40有效负载远小于静脉内（IV）免疫疗法所需的效果。 该项目的总体目标——由 Nanocan Therapeutics Corporation 与 John 合作提出 霍普金斯医学院、丹娜法伯癌症研究所和诺斯韦尔健康中心 - 将临床前工作与第一阶段联系起来 采用创新的 RAID 技术进行临床试验，并确认其可延长原位疫苗接种的潜力 使用放射治疗 (RT) 在一次疗程中从姑息性局部治疗到全身疾病控制。 iSRB 作为种子状基准标记，通过超声引导直接施用到前列腺肿瘤中 针。 iSRB 可在 CT 和 KV 成像上产生对比度，从而使 RT 设置快速； iSRB 缓慢释放（20mcg 每单位超过 15 天）抗 CD40 有效负载直接照射到受辐射的目标，触发原位疫苗接种。 该项目的目的是转化来自单一药物小动物研究的广泛安全性和有效性数据 首次针对 CRPC 患者的人体试验采用分次放疗联合缓慢释放的肿瘤内抗 CD40 递送。 第一部分将用于将 iSRB 优化为 cGMP 产品，并确认在 猴子确认安全性、免疫原性和药代动力学已在广泛的小动物中进行 工作。 Milestones 将由 Nanocan Therapeutics 完成 IND 申报。 FDA批准后，第二部分 项目将包括第一阶段单臂开放标签临床试验，寻求安全性和数量的确认 iSRB 的数量以及 CRPR 患者所需的 RT 剂量。该项目可以提供计划所需的所有数据 II 期临床工作旨在为 CRPR 患者提供一种新的治疗范例。